FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3100448112> ?p ?o ?g. }

• W3100448112 abstract "Abstract Background Imatinib is mainly metabolized by CYP3A4 and to a lesser extent by other isoenzymes, with N -desmethyl imatinib being its major equipotent metabolite. Being a CYP3A4 substrate, imatinib co-administration with CYP3A4 modulators would change its pharmacokinetic profile. The cancer chemoprevention potential and anticancer efficacy of many herbal products such as grape seed (GS) and green tea (GT) extracts had led to an increase in their concomitant use with anticancer agents. GS and GT extracts were demonstrated to be potent inhibitors of CYP3A4. The aim of this study is to investigate the effect of standardized GS and/or GT extracts at two different doses on the pharmacokinetics of imatinib and its metabolite, N -desmethyl imatinib, in SD-rats. Methods Standardized GS and/or GT extracts were administered orally once daily for 21 days, at low ( l ) and high ( h ) doses, 50 and 100 mg/kg, respectively, before the administration of a single intragastric dose of imatinib. Plasma samples were collected and analyzed for imatinib and N -desmethyl imatinib concentrations using LC-MS/MS method, then their non-compartmental pharmacokinetic parameters were determined. Results h -GS dose significantly decreased imatinib’s C max and the $$ {mathrm{AUC}}_0^{infty } $$ <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML><mml:msubsup><mml:mi>AUC</mml:mi><mml:mn>0</mml:mn><mml:mo>∞</mml:mo></mml:msubsup></mml:math> by 61.1 and 72.2%, respectively. Similar effects on N -desmethyl imatinib’s exposure were observed as well, in addition to a significant increase in its clearance by 3.7-fold. l -GT caused a significant decrease in imatinib’s C max and $$ {mathrm{AUC}}_0^{infty } $$ <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML><mml:msubsup><mml:mi>AUC</mml:mi><mml:mn>0</mml:mn><mml:mo>∞</mml:mo></mml:msubsup></mml:math> by 53.6 and 63.5%, respectively, with more significant effects on N -desmethyl imatinib’s exposure, which exhibited a significant decrease by 79.2 and 81.1%, respectively. h -GT showed similar effects as those of l -GT on the kinetics of imatinib and its metabolite. However, when these extracts were co-administered at low doses, no significant effects were shown on the pharmacokinetics of imatinib and its metabolite. Nevertheless, increasing the dose caused a significant decrease in C max of N -desmethyl imatinib by 71.5%. Conclusions These results demonstrated that the pharmacokinetics of imatinib and N -desmethyl imatinib had been significantly affected by GS and/or GT extracts, which could be partially explained by the inhibition of CYP3A-mediated metabolism. However, the involvement of other kinetic pathways such as other isoenzymes, efflux and uptake transporters could be involved and should be characterized. Graphical abstract" @default.
• W3100448112 created "2020-11-23" @default.
• W3100448112 creator A5003494563 @default.
• W3100448112 creator A5011361603 @default.
• W3100448112 creator A5015444662 @default.
• W3100448112 creator A5024253681 @default.
• W3100448112 creator A5033752774 @default.
• W3100448112 creator A5053777609 @default.
• W3100448112 creator A5090658870 @default.
• W3100448112 date "2020-11-16" @default.
• W3100448112 modified "2023-10-17" @default.
• W3100448112 title "The effect of grape seed and green tea extracts on the pharmacokinetics of imatinib and its main metabolite, N-desmethyl imatinib, in rats" @default.
• W3100448112 cites W1547782763 @default.
• W3100448112 cites W1554374902 @default.
• W3100448112 cites W1561510118 @default.
• W3100448112 cites W1581887873 @default.
• W3100448112 cites W1728621917 @default.
• W3100448112 cites W1861068788 @default.
• W3100448112 cites W1868407335 @default.
• W3100448112 cites W1909149359 @default.
• W3100448112 cites W1909383564 @default.
• W3100448112 cites W1914622032 @default.
• W3100448112 cites W1966300288 @default.
• W3100448112 cites W1967773734 @default.
• W3100448112 cites W1968826699 @default.
• W3100448112 cites W1973075736 @default.
• W3100448112 cites W1974077091 @default.
• W3100448112 cites W1977526476 @default.
• W3100448112 cites W1977668530 @default.
• W3100448112 cites W1979437347 @default.
• W3100448112 cites W1983171777 @default.
• W3100448112 cites W1985758966 @default.
• W3100448112 cites W1991091713 @default.
• W3100448112 cites W1995514723 @default.
• W3100448112 cites W2000519650 @default.
• W3100448112 cites W2003640047 @default.
• W3100448112 cites W2009429426 @default.
• W3100448112 cites W2010124690 @default.
• W3100448112 cites W2015408483 @default.
• W3100448112 cites W2020520400 @default.
• W3100448112 cites W2024962401 @default.
• W3100448112 cites W2026260853 @default.
• W3100448112 cites W2027128842 @default.
• W3100448112 cites W2028959752 @default.
• W3100448112 cites W2029310284 @default.
• W3100448112 cites W2030873577 @default.
• W3100448112 cites W2031661886 @default.
• W3100448112 cites W2031789773 @default.
• W3100448112 cites W2032011566 @default.
• W3100448112 cites W2033085346 @default.
• W3100448112 cites W2034074778 @default.
• W3100448112 cites W2036188065 @default.
• W3100448112 cites W2036542307 @default.
• W3100448112 cites W2036956314 @default.
• W3100448112 cites W2037398716 @default.
• W3100448112 cites W2041801408 @default.
• W3100448112 cites W2042579252 @default.
• W3100448112 cites W2043303252 @default.
• W3100448112 cites W2050275393 @default.
• W3100448112 cites W2052190542 @default.
• W3100448112 cites W2054458894 @default.
• W3100448112 cites W2056870981 @default.
• W3100448112 cites W2061860992 @default.
• W3100448112 cites W2072641576 @default.
• W3100448112 cites W2073260913 @default.
• W3100448112 cites W2080563407 @default.
• W3100448112 cites W2088265246 @default.
• W3100448112 cites W2090894363 @default.
• W3100448112 cites W2092754641 @default.
• W3100448112 cites W2092796573 @default.
• W3100448112 cites W2094670792 @default.
• W3100448112 cites W2097466434 @default.
• W3100448112 cites W2100046156 @default.
• W3100448112 cites W2101577669 @default.
• W3100448112 cites W2104487496 @default.
• W3100448112 cites W2105697161 @default.
• W3100448112 cites W2105831683 @default.
• W3100448112 cites W2106142215 @default.
• W3100448112 cites W2110901518 @default.
• W3100448112 cites W2112158545 @default.
• W3100448112 cites W2116060738 @default.
• W3100448112 cites W2118324262 @default.
• W3100448112 cites W2119880272 @default.
• W3100448112 cites W2120098852 @default.
• W3100448112 cites W2121587436 @default.
• W3100448112 cites W2121856284 @default.
• W3100448112 cites W2124816030 @default.
• W3100448112 cites W2125205249 @default.
• W3100448112 cites W2128679009 @default.
• W3100448112 cites W2132100195 @default.
• W3100448112 cites W2132176892 @default.
• W3100448112 cites W2132656575 @default.
• W3100448112 cites W2141081902 @default.
• W3100448112 cites W2152940859 @default.
• W3100448112 cites W2155229204 @default.
• W3100448112 cites W2157380551 @default.
• W3100448112 cites W2158735110 @default.
• W3100448112 cites W2159693812 @default.
• W3100448112 cites W2209081542 @default.
• W3100448112 cites W2290466312 @default.

• next